Considerations for nonsteroidal anti-inflammatory drug therapy: safety.

Although therapeutically beneficial, nonsteroidal anti-inflammatory drugs are associated with serious gastrointestinal side effects, including ulceration, hemorrhage, and perforation. Endoscopic studies indicate that up to 30% of chronic NSAID users will develop gastroduodenal ulceration. Various case-control studies have reported an association between ulcer-related complications or deaths and NSAID use. An imprecise correlation has been found to exist between the presence of NSAID-induced gastrointestinal damage and symptoms, such as dyspepsia and pain. It is now thought that the major deleterious effects of NSAIDs on the gastrointestinal tract are related to the ability of systemically absorbed NSAIDs to alter gastric and duodenal defense mechanisms, primarily via inhibition of mucosal prostaglandin synthesis. Although various therapeutic agents have been investigated for their ability to prevent NSAID-induced ulcers, only the prostaglandin analogue misoprostol has been shown to significantly reduce the incidence of both gastric and duodenal ulcers in NSAID users. Recently, the Misoprostol Ulcer Complications Outcomes Safety Assessment trial demonstrated that misoprostol also reduces the most serious complications of NSAID-induced ulcers, namely bleeding, perforation, and gastric outlet obstruction.